This project is essentially a continuation of previous Grant MH-14110 dealing with the pharmacology of synaptic transmission and modulation. Our aim is to study the possible role of a series of compounds related to the classical biogenic amines known or suspected to be present in brain tissue. They include the amino acid precursors (DOPA, 5-hydroxytryptophan), the less hydroxylated dreivatives (2-phenylethylamine, tryptamine, octopamine), and the metabolites (5-hydroxyindoleacetaldehyde, 5-hydroxyindoleacetic acid, normetanephrine) or catecholamines and serotonin, as well as another important amine histamine. The electrophysiological studies are primarily concerned with cortical and caudate evoked responses to electrical stimulation and to sensory stimulation in rabbits, recorded by means of macroelectrodes and extracellular micropipettes; drugs will be administered systemically or by microiontophroesis. The behavioral functions studied include sleep, motor activity, rage and hallucinatory-like patterns, and neurological observations. Biochemical studies will include the identification and quaatfication of the substances under study, attempting to correlate their brain levels and turnover to physiological and behavioral parameters. The particular strategy of this research will be to test for the biological effect and functional significance of a series of biogenic amines and related amino acids and metabolites (aldehyde, alcoholic, etc.) which are known to be present in the brain and to examine their interactions with behaviorally active drugs.